001 METHODOLOGICAL APPROACHES TO GENE–ENVIRONMENT INTERACTIONS IN OCCUPATIONAL EPIDEMIOLOGY

There are several aspects that are still unresolved in the study of gene–environment interactions (GEI), particularly in the occupational setting.

Errors of measurement:

Measurements of genes (genotyping) and of environmental agents are usually prone to error to different degrees. Genotyping is in general more accurate than the majority of methods used to measure environmental exposures. This implies a lower degree of classification errors that in turn means an easier identification of associations with disease. Unless the size of the studies is calculated to achieve an adequate power of detection for associations of disease with the variables most affected by classification errors, that is, the environmental ones (diet, job titles, pollutants, etc), it can be safely predicted that such studies will come up with a number of genetic associations but very few credible environmental associations with disease. In addition, as the majority of genetic polymorphisms are believed to act through biological interaction with environmental agents, it may also become difficult to make sense of genetic observations if the environmental component is substantially misclassified.

Testing of multiple hypotheses:

While accurate genotyping measurement makes easier the detection of gene–disease associations, it also contributes to enhance the chance of false positive results if, as is more and more the case, associations between each of hundred or thousands of genetic variants and disease phenotype are tested. In the light of reasonable assumptions on the …